CA2691638A1 - Derives de piperidine utiles comme antagonistes vis-avis des recepteurs de l'orexine - Google Patents

Info

Publication number

CA2691638A1

CA2691638A1 CA002691638A CA2691638A CA2691638A1 CA 2691638 A1 CA2691638 A1 CA 2691638A1 CA 002691638 A CA002691638 A CA 002691638A CA 2691638 A CA2691638 A CA 2691638A CA 2691638 A1 CA2691638 A1 CA 2691638A1

Authority

CA

Canada

Prior art keywords

methyl

disorder

alkyl

imidazo

pyridine

Prior art date

2007-07-03

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Abandoned

Links

• Espacenet
• Global Dossier
• CIPO
• Discuss

• 150000003053 piperidines Chemical class 0.000 title abstract description 6
• 229940123730 Orexin receptor antagonist Drugs 0.000 title description 5
• 238000011282 treatment Methods 0.000 claims abstract description 24
• 239000003814 drug Substances 0.000 claims abstract description 12
• 150000001875 compounds Chemical class 0.000 claims description 253
• 150000003839 salts Chemical class 0.000 claims description 123
• 125000005843 halogen group Chemical group 0.000 claims description 92
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 85
• 125000000217 alkyl group Chemical group 0.000 claims description 63
• 208000019116 sleep disease Diseases 0.000 claims description 56
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 46
• 208000035475 disorder Diseases 0.000 claims description 46
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 45
• 238000000034 method Methods 0.000 claims description 41
• 201000010099 disease Diseases 0.000 claims description 39
• 208000020685 sleep-wake disease Diseases 0.000 claims description 32
• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 25
• 208000020016 psychiatric disease Diseases 0.000 claims description 23
• 102000008834 Orexin receptor Human genes 0.000 claims description 22
• 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 claims description 22
• 239000005557 antagonist Substances 0.000 claims description 22
• 206010022437 insomnia Diseases 0.000 claims description 22
• 208000019901 Anxiety disease Diseases 0.000 claims description 21
• 208000006199 Parasomnias Diseases 0.000 claims description 21
• 206010020765 hypersomnia Diseases 0.000 claims description 21
• 101000598921 Homo sapiens Orexin Proteins 0.000 claims description 19
• 125000001153 fluoro group Chemical group F* 0.000 claims description 19
• 208000019022 Mood disease Diseases 0.000 claims description 17
• 208000007590 Disorders of Excessive Somnolence Diseases 0.000 claims description 14
• 206010013980 Dyssomnias Diseases 0.000 claims description 14
• 208000011117 substance-related disease Diseases 0.000 claims description 13
• 125000004857 imidazopyridinyl group Chemical group N1C(=NC2=C1C=CC=N2)* 0.000 claims description 12
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 10
• GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 claims description 9
• 208000019454 Feeding and Eating disease Diseases 0.000 claims description 8
• 208000021500 Breathing-related sleep disease Diseases 0.000 claims description 7
• 208000019888 Circadian rhythm sleep disease Diseases 0.000 claims description 7
• 208000016588 Idiopathic hypersomnia Diseases 0.000 claims description 7
• 208000001456 Jet Lag Syndrome Diseases 0.000 claims description 7
• 208000019693 Lung disease Diseases 0.000 claims description 7
• 208000012902 Nervous system disease Diseases 0.000 claims description 7
• 208000025966 Neurological disease Diseases 0.000 claims description 7
• 208000000224 Night Terrors Diseases 0.000 claims description 7
• 206010029412 Nightmare Diseases 0.000 claims description 7
• 208000005793 Restless legs syndrome Diseases 0.000 claims description 7
• 206010063910 Sleep disorder due to a general medical condition Diseases 0.000 claims description 7
• 206010041347 Somnambulism Diseases 0.000 claims description 7
• 208000019622 heart disease Diseases 0.000 claims description 7
• 201000003631 narcolepsy Diseases 0.000 claims description 7
• 208000004296 neuralgia Diseases 0.000 claims description 7
• 208000021722 neuropathic pain Diseases 0.000 claims description 7
• 239000008194 pharmaceutical composition Substances 0.000 claims description 7
• 201000002859 sleep apnea Diseases 0.000 claims description 7
• 208000022925 sleep disturbance Diseases 0.000 claims description 7
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 7
• 229910052736 halogen Chemical group 0.000 claims description 6
• 150000002367 halogens Chemical group 0.000 claims description 6
• 125000002346 iodo group Chemical group I* 0.000 claims description 6
• 239000003937 drug carrier Substances 0.000 claims description 5
• 238000002560 therapeutic procedure Methods 0.000 claims description 5
• 125000003342 alkenyl group Chemical group 0.000 claims description 4
• 238000004519 manufacturing process Methods 0.000 claims description 3
• 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 2
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims 80
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 43
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims 40
• 208000018460 Feeding disease Diseases 0.000 claims 6
• QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 claims 1
• 208000008589 Obesity Diseases 0.000 abstract description 8
• 235000020824 obesity Nutrition 0.000 abstract description 8
• 206010012601 diabetes mellitus Diseases 0.000 abstract description 6
• 125000006514 pyridin-2-ylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 abstract 1
• 239000000203 mixture Substances 0.000 description 230
• 239000000243 solution Substances 0.000 description 159
• YMWUJEATGCHHMB-UHFFFAOYSA-N dichloromethane Natural products ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 153
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Natural products CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 106
• 238000004704 ultra performance liquid chromatography Methods 0.000 description 101
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 75
• 238000003756 stirring Methods 0.000 description 75
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 66
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 64
• 239000002904 solvent Substances 0.000 description 61
• 239000007787 solid Substances 0.000 description 59
• 238000005481 NMR spectroscopy Methods 0.000 description 58
• 235000019439 ethyl acetate Nutrition 0.000 description 53
• 239000011541 reaction mixture Substances 0.000 description 51
• 238000004128 high performance liquid chromatography Methods 0.000 description 50
• 238000001819 mass spectrum Methods 0.000 description 50
• -1 imidazo[1,2-a]pyridin-2-ylmethyl Chemical group 0.000 description 49
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 48
• 239000003921 oil Substances 0.000 description 44
• 235000019198 oils Nutrition 0.000 description 44
• 239000007864 aqueous solution Substances 0.000 description 43
• 239000012458 free base Substances 0.000 description 43
• 238000006243 chemical reaction Methods 0.000 description 42
• 239000000741 silica gel Substances 0.000 description 41
• 229910002027 silica gel Inorganic materials 0.000 description 41
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 39
• 238000003818 flash chromatography Methods 0.000 description 38
• 238000000746 purification Methods 0.000 description 38
• DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 37
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 36
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 35
• 239000000463 material Substances 0.000 description 35
• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 30
• 239000012071 phase Substances 0.000 description 30
• 102000005962 receptors Human genes 0.000 description 30
• 108020003175 receptors Proteins 0.000 description 30
• ZIJCVCKVXHYUPU-JTQLQIEISA-N tert-butyl (2s)-2-(3-bromo-2-oxopropyl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCC[C@H]1CC(=O)CBr ZIJCVCKVXHYUPU-JTQLQIEISA-N 0.000 description 29
• UTCSSFWDNNEEBH-UHFFFAOYSA-N imidazo[1,2-a]pyridine Chemical compound C1=CC=CC2=NC=CN21 UTCSSFWDNNEEBH-UHFFFAOYSA-N 0.000 description 28
• 239000012267 brine Substances 0.000 description 27
• 239000012074 organic phase Substances 0.000 description 27
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 27
• 239000003039 volatile agent Substances 0.000 description 27
• IUPHMHDVSPSLME-UHFFFAOYSA-N 2-methyl-5-phenyl-1,3-thiazole-4-carboxylic acid Chemical class S1C(C)=NC(C(O)=O)=C1C1=CC=CC=C1 IUPHMHDVSPSLME-UHFFFAOYSA-N 0.000 description 26
• 125000003545 alkoxy group Chemical group 0.000 description 26
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 25
• 210000004027 cell Anatomy 0.000 description 24
• 239000012044 organic layer Substances 0.000 description 24
• 101150041968 CDC13 gene Proteins 0.000 description 22
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 22
• WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 20
• XAGWZZFXYPQHJH-ZETCQYMHSA-N (2S)-2-(3-bromo-2-oxopropyl)piperidine-1-carboxylic acid Chemical compound OC(=O)N1CCCC[C@H]1CC(=O)CBr XAGWZZFXYPQHJH-ZETCQYMHSA-N 0.000 description 17
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical class C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 15
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
• 150000001263 acyl chlorides Chemical class 0.000 description 15
• 231100000566 intoxication Toxicity 0.000 description 15
• 230000035987 intoxication Effects 0.000 description 15
• 239000000725 suspension Substances 0.000 description 15
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
• JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 14
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
• 102000002512 Orexin Human genes 0.000 description 13
• 239000012317 TBTU Substances 0.000 description 13
• CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 13
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 13
• 239000000047 product Substances 0.000 description 13
• 239000003446 ligand Substances 0.000 description 12
• 108060005714 orexin Proteins 0.000 description 12
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 11
• 206010012218 Delirium Diseases 0.000 description 11
• 241000700159 Rattus Species 0.000 description 11
• 238000002360 preparation method Methods 0.000 description 11
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 10
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
• 239000013058 crude material Substances 0.000 description 10
• BGMUHNGEMIPVIY-UHFFFAOYSA-N 5-fluoro-3-methylpyridin-2-amine Chemical compound CC1=CC(F)=CN=C1N BGMUHNGEMIPVIY-UHFFFAOYSA-N 0.000 description 9
• 208000028017 Psychotic disease Diseases 0.000 description 9
• 239000010779 crude oil Substances 0.000 description 9
• 239000010410 layer Substances 0.000 description 9
• 238000011321 prophylaxis Methods 0.000 description 9
• 239000000556 agonist Substances 0.000 description 8
• 238000004587 chromatography analysis Methods 0.000 description 8
• NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 8
• MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 8
• BSSPNISMQJMZBJ-UHFFFAOYSA-N 3-(2,2,2-trifluoroethoxy)pyridin-2-amine Chemical compound NC1=NC=CC=C1OCC(F)(F)F BSSPNISMQJMZBJ-UHFFFAOYSA-N 0.000 description 7
• RZJPBQGRCNJYBU-UHFFFAOYSA-N 3-chloropyridin-2-amine Chemical compound NC1=NC=CC=C1Cl RZJPBQGRCNJYBU-UHFFFAOYSA-N 0.000 description 7
• APNYUCFJXZVKAI-UHFFFAOYSA-N 3-ethenyl-5-fluoropyridin-2-amine Chemical compound NC1=NC=C(F)C=C1C=C APNYUCFJXZVKAI-UHFFFAOYSA-N 0.000 description 7
• HNAYRVKSWGSQTP-UHFFFAOYSA-N 3-methoxypyridin-2-amine Chemical compound COC1=CC=CN=C1N HNAYRVKSWGSQTP-UHFFFAOYSA-N 0.000 description 7
• YWPRTLLHPBPDBE-UHFFFAOYSA-N 5-fluoro-3-(methoxymethyl)pyridin-2-amine Chemical compound COCC1=CC(F)=CN=C1N YWPRTLLHPBPDBE-UHFFFAOYSA-N 0.000 description 7
• 238000012216 screening Methods 0.000 description 7
• 239000007858 starting material Substances 0.000 description 7
• FYHQEGIVKQGQHC-UHFFFAOYSA-N (2-chloro-5-fluoropyridin-3-yl)methanol Chemical compound OCC1=CC(F)=CN=C1Cl FYHQEGIVKQGQHC-UHFFFAOYSA-N 0.000 description 6
• YBZCGMAFKGACDB-LBPRGKRZSA-N 8-methyl-2-[[(2s)-piperidin-2-yl]methyl]imidazo[1,2-a]pyridine Chemical compound N1=C2C(C)=CC=CN2C=C1C[C@@H]1CCCCN1 YBZCGMAFKGACDB-LBPRGKRZSA-N 0.000 description 6
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
• BDAGIHXWWSANSR-UHFFFAOYSA-N Formic acid Chemical compound OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
• 241000721701 Lynx Species 0.000 description 6
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 6
• 108050000742 Orexin Receptor Proteins 0.000 description 6
• 201000001880 Sexual dysfunction Diseases 0.000 description 6
• 238000004458 analytical method Methods 0.000 description 6
• 239000002249 anxiolytic agent Substances 0.000 description 6
• 230000000949 anxiolytic effect Effects 0.000 description 6
• 239000012300 argon atmosphere Substances 0.000 description 6
• MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 6
• 238000001914 filtration Methods 0.000 description 6
• 230000000147 hypnotic effect Effects 0.000 description 6
• MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
• OFNHNCAUVYOTPM-IIIOAANCSA-N orexin-a Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)[C@H](C)NC(=O)CNC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H]1NC(=O)[C@H](CO)NC(=O)[C@@H]2CSSC[C@@H](C(=O)N[C@H](C(N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N2)[C@@H](C)O)=O)CSSC1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC(C)C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H]1NC(=O)CC1)C1=CNC=N1 OFNHNCAUVYOTPM-IIIOAANCSA-N 0.000 description 6
• 239000002245 particle Substances 0.000 description 6
• 239000000932 sedative agent Substances 0.000 description 6
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• 231100000872 sexual dysfunction Toxicity 0.000 description 6
• 238000006467 substitution reaction Methods 0.000 description 6
• WTBIBIJFMBUHGC-AWEZNQCLSA-N tert-butyl (2s)-2-[(8-fluoroimidazo[1,2-a]pyridin-2-yl)methyl]piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCC[C@H]1CC1=CN(C=CC=C2F)C2=N1 WTBIBIJFMBUHGC-AWEZNQCLSA-N 0.000 description 6
• 238000012360 testing method Methods 0.000 description 6
• KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 description 5
• ZUOOPVNOZFXEJY-JTQLQIEISA-N 2-[[(2s)-piperidin-2-yl]methyl]-5-(trifluoromethyl)imidazo[1,2-a]pyridine Chemical compound C=1N2C(C(F)(F)F)=CC=CC2=NC=1C[C@@H]1CCCCN1 ZUOOPVNOZFXEJY-JTQLQIEISA-N 0.000 description 5
• PITFQOXKTLFYDZ-NSHDSACASA-N 2-[[(2s)-piperidin-2-yl]methyl]-6-(trifluoromethyl)imidazo[1,2-a]pyridine Chemical compound C=1N2C=C(C(F)(F)F)C=CC2=NC=1C[C@@H]1CCCCN1 PITFQOXKTLFYDZ-NSHDSACASA-N 0.000 description 5
• GCPDFSCANDNQPZ-UHFFFAOYSA-N 2-chloro-3-ethenyl-5-fluoropyridine Chemical compound FC1=CN=C(Cl)C(C=C)=C1 GCPDFSCANDNQPZ-UHFFFAOYSA-N 0.000 description 5
• YLLPKZZZTACMIO-UHFFFAOYSA-N 2-chloro-5-fluoro-3-methoxypyridine Chemical compound COC1=CC(F)=CN=C1Cl YLLPKZZZTACMIO-UHFFFAOYSA-N 0.000 description 5
• FMPYGEFGXUAAKG-UHFFFAOYSA-N 2-chloro-5-fluoro-3-methylpyridine Chemical compound CC1=CC(F)=CN=C1Cl FMPYGEFGXUAAKG-UHFFFAOYSA-N 0.000 description 5
• ZTRVHUJTCWJLEL-JTQLQIEISA-N 3-chloro-2-[[(2s)-piperidin-2-yl]methyl]-7-(trifluoromethyl)imidazo[1,2-a]pyridine Chemical compound N1=C2C=C(C(F)(F)F)C=CN2C(Cl)=C1C[C@@H]1CCCCN1 ZTRVHUJTCWJLEL-JTQLQIEISA-N 0.000 description 5
• YOLAMLOJYNERJQ-JTQLQIEISA-N 3-chloro-2-[[(2s)-piperidin-2-yl]methyl]imidazo[1,2-a]pyridine Chemical compound N1=C2C=CC=CN2C(Cl)=C1C[C@@H]1CCCCN1 YOLAMLOJYNERJQ-JTQLQIEISA-N 0.000 description 5
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